MATR3

Summary

MATR3 (matrin 3, HGNC:6912) is a protein-coding gene on chromosome 5q31.2, encoding Matrin-3 (P43243). May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. It is a selective cancer dependency (DepMap: 14.6% of cell lines).

This gene encodes a nuclear matrix protein, which is proposed to stabilize certain messenger RNA species. Mutations of this gene are associated with distal myopathy 2, which often includes vocal cord and pharyngeal weakness. Alternatively spliced transcript variants, including read-through transcripts composed of the upstream small nucleolar RNA host gene 4 (non-protein coding) and matrin 3 gene sequence, have been identified. Pseudogenes of this gene are located on chromosomes 1 and X.

Source: NCBI Gene 9782 — RefSeq curated summary.

At a glance

• Gene–disease (curated): distal myopathy with vocal cord weakness (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 627 total — 1 pathogenic (top 5% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 9 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 20 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 85
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 14.6% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.12 (highly constrained)
• MANE Select transcript: NM_018834
• Interaction hub: 2,222 STRING partners (top 6% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6912
Approved symbol	MATR3
Name	matrin 3
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0723, MGC9105, VCPDM
Ensembl gene	ENSG00000015479
Ensembl biotype	protein_coding
OMIM	164015
Entrez	9782

Gene structure

Transcript identifiers

Ensembl transcripts: 93 — 80 protein_coding, 8 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000394805

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 11, TSL 3: 6, TSL 4: 11, TSL 5: 6

ENST00000394805, ENST00000361059, ENST00000394800, ENST00000502394, ENST00000502422, ENST00000502499, ENST00000502929, ENST00000502944, ENST00000503340, ENST00000503811, ENST00000504023, ENST00000504045, ENST00000504203, ENST00000504311, ENST00000504643, ENST00000505016, ENST00000505625, ENST00000506147, ENST00000507860, ENST00000508689, ENST00000509644, ENST00000509918, ENST00000509990, ENST00000510056, ENST00000511249, ENST00000511333, ENST00000511978, ENST00000512040, ENST00000512107, ENST00000512876, ENST00000513121, ENST00000513678, ENST00000514402, ENST00000514488, ENST00000514528, ENST00000514694, ENST00000515833, ENST00000618441, ENST00000910013, ENST00000910014, ENST00000910015, ENST00000910016, ENST00000910017, ENST00000910018, ENST00000910019, ENST00000910020, ENST00000910021, ENST00000910022, ENST00000910023, ENST00000910024, ENST00000910025, ENST00000910026, ENST00000910027, ENST00000910028, ENST00000910029, ENST00000910030, ENST00000910031, ENST00000928206, ENST00000928207, ENST00000928208, ENST00000928209, ENST00000928210, ENST00000928211, ENST00000955711, ENST00000955712, ENST00000955713, ENST00000955714, ENST00000955715, ENST00000955716, ENST00000955717, ENST00001037424, ENST00001037425, ENST00001037426, ENST00001037427, ENST00001037428, ENST00001037429, ENST00001037430, ENST00001037431, ENST00001037432, ENST00001037433, ENST00001037434, ENST00001037439, ENST00001037447, ENST00001037448, ENST00001087512, ENST00001087513, ENST00001087514, ENST00001087515, ENST00001087516, ENST00001087517, ENST00001087519, ENST00001116463, ENST00001136948

RefSeq mRNA: 31 — MANE Select: NM_018834 NM_001194954, NM_001194955, NM_001194956, NM_001282278, NM_001400441, NM_001400442, NM_001400443, NM_001400444, NM_001400445, NM_001400447, NM_001400448, NM_001400450, NM_001400451, NM_001400452, NM_001400453, NM_001400454, NM_001400455, NM_001400456, NM_001400457, NM_001400458, NM_001400459, NM_001400460, NM_001400461, NM_001400462, NM_001400463, NM_001400464, NM_001400465, NM_001400466, NM_001400467, NM_018834, NM_199189

CCDS: CCDS54908, CCDS93789

Canonical transcript exons

ENST00000394805 — 15 exons

Exon	Start	End
ENSE00001407316	139329345	139331677
ENSE00002070863	139293740	139293805
ENSE00003760488	139318908	139319033
ENSE00003761810	139326163	139326284
ENSE00003763930	139322598	139322967
ENSE00003765763	139316076	139316188
ENSE00003766231	139321898	139322029
ENSE00003766301	139315697	139315738
ENSE00003766452	139317053	139317105
ENSE00003766880	139322463	139322506
ENSE00003768957	139319334	139319501
ENSE00003769838	139325440	139325662
ENSE00003771240	139317596	139317721
ENSE00003772093	139307239	139308327
ENSE00003775312	139314675	139314736

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 99.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 152.1080 / max 2353.9927, expressed in 1823 samples.

Highest expression (Bgee): cortical plate, corpus callosum, ganglionic eminence, ventricular zone, calcaneal tendon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MATR3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	3.3e-05	+0.27	5:139348872:C:T
Nerve Tibial	eqtl	1.3e-04	-0.18	5:139369899:A:G
Adrenal Gland	eqtl	2.1e-03	-0.26	5:139374887:G:C
Skin Sun Exposed Lower leg	eqtl	2.9e-03	+0.16	5:139383136:C:G
Brain Cerebellar Hemisphere	eqtl	3.8e-03	-0.90	5:139330471:T:C
Brain Amygdala	eqtl	4.6e-03	+1.71	5:138706085:T:C
Brain Cortex	eqtl	6.8e-03	+0.82	5:138740258:T:C
Esophagus Mucosa	eqtl	1.1e-02	-0.16	5:139564105:T:C
Adipose Subcutaneous	eqtl	1.4e-02	+0.14	5:139439612:C:T
Cells Cultured fibroblasts	sqtl	1.9e-02	+0.21	5:139302450:T:C
Esophagus Muscularis	eqtl	2.2e-02	-0.60	5:138740258:T:C
Cells Cultured fibroblasts	eqtl	2.3e-02	+0.16	5:139448045:A:G
Stomach	eqtl	2.3e-02	-0.76	5:139330471:T:C
Brain Hypothalamus	sqtl	2.4e-02	+1.48	5:138934687:A:T
Brain Nucleus accumbens basal ganglia	eqtl	2.5e-02	+0.83	5:138987603:A:T
Colon Transverse	eqtl	2.7e-02	+0.66	5:138987603:A:T
Skin Not Sun Exposed Suprapubic	eqtl	2.8e-02	+0.13	5:139235203:A:T
Brain Hippocampus	eqtl	3.4e-02	+0.46	5:139170549:C:T
Breast Mammary Tissue	eqtl	3.5e-02	-0.19	5:138663715:C:G
Artery Tibial	eqtl	3.8e-02	+0.11	5:139109237:A:G

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
58814	91.2912	1822
58815	29.4172	1777
58812	16.9571	1785
58813	12.4562	1747
58808	11.0268	1709
58807	0.7331	163
58822	0.3725	151
58817	0.3646	161
203708	0.2666	87
58816	0.2495	90

Top tissues by expression

showing 100 of 138 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.64	gold quality
corpus callosum	UBERON:0002336	99.62	gold quality
ganglionic eminence	UBERON:0004023	99.58	gold quality
ventricular zone	UBERON:0003053	99.55	gold quality
calcaneal tendon	UBERON:0003701	99.50	gold quality
superior frontal gyrus	UBERON:0002661	99.36	gold quality
endometrium	UBERON:0001295	99.25	gold quality
primary visual cortex	UBERON:0002436	99.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.15	gold quality
adrenal tissue	UBERON:0018303	99.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.09	gold quality
colonic epithelium	UBERON:0000397	99.07	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.05	gold quality
prefrontal cortex	UBERON:0000451	99.02	gold quality
smooth muscle tissue	UBERON:0001135	98.92	gold quality
cerebellar hemisphere	UBERON:0002245	98.90	gold quality
cerebellar cortex	UBERON:0002129	98.84	gold quality
tonsil	UBERON:0002372	98.83	gold quality
cerebral cortex	UBERON:0000956	98.81	gold quality
cerebellum	UBERON:0002037	98.81	gold quality
lymph node	UBERON:0000029	98.80	gold quality
nucleus accumbens	UBERON:0001882	98.80	gold quality
ovary	UBERON:0000992	98.73	gold quality
hypothalamus	UBERON:0001898	98.72	gold quality
islet of Langerhans	UBERON:0000006	98.71	gold quality
frontal cortex	UBERON:0001870	98.71	gold quality
left ovary	UBERON:0002119	98.69	gold quality
brain	UBERON:0000955	98.68	gold quality
gall bladder	UBERON:0002110	98.67	gold quality
Ammon’s horn	UBERON:0001954	98.65	gold quality
amygdala	UBERON:0001876	98.64	gold quality
caudate nucleus	UBERON:0001873	98.63	gold quality
anterior cingulate cortex	UBERON:0009835	98.62	gold quality
fallopian tube	UBERON:0003889	98.61	gold quality
putamen	UBERON:0001874	98.60	gold quality
stromal cell of endometrium	CL:0002255	98.59	gold quality
temporal lobe	UBERON:0001871	98.58	gold quality
right ovary	UBERON:0002118	98.53	gold quality
body of uterus	UBERON:0009853	98.52	gold quality
endocervix	UBERON:0000458	98.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.48	gold quality
uterine cervix	UBERON:0000002	98.43	gold quality
rectum	UBERON:0001052	98.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.37	gold quality
descending thoracic aorta	UBERON:0002345	98.33	gold quality
substantia nigra	UBERON:0002038	98.32	gold quality
right frontal lobe	UBERON:0002810	98.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.31	gold quality
myometrium	UBERON:0001296	98.29	gold quality
bone marrow	UBERON:0002371	98.29	gold quality
urinary bladder	UBERON:0001255	98.28	gold quality
pancreas	UBERON:0001264	98.28	gold quality
bone marrow cell	CL:0002092	98.25	gold quality
mucosa of stomach	UBERON:0001199	98.25	gold quality
thyroid gland	UBERON:0002046	98.25	gold quality
right uterine tube	UBERON:0001302	98.24	gold quality
spinal cord	UBERON:0002240	98.23	gold quality
ectocervix	UBERON:0012249	98.23	gold quality
popliteal artery	UBERON:0002250	98.22	gold quality
placenta	UBERON:0001987	98.21	gold quality
tibial artery	UBERON:0007610	98.21	gold quality
left uterine tube	UBERON:0001303	98.19	gold quality
left lobe of thyroid gland	UBERON:0001120	98.16	gold quality
right lobe of thyroid gland	UBERON:0001119	98.15	gold quality
tibial nerve	UBERON:0001323	98.14	gold quality
body of pancreas	UBERON:0001150	98.12	gold quality
vermiform appendix	UBERON:0001154	98.12	gold quality
right coronary artery	UBERON:0001625	98.12	gold quality
right lung	UBERON:0002167	98.09	gold quality
thoracic mammary gland	UBERON:0005200	98.06	gold quality
thoracic aorta	UBERON:0001515	97.98	gold quality
adenohypophysis	UBERON:0002196	97.98	gold quality
pituitary gland	UBERON:0000007	97.95	gold quality
ascending aorta	UBERON:0001496	97.94	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.92	gold quality
adrenal gland	UBERON:0002369	97.91	gold quality
monocyte	CL:0000576	97.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.90	gold quality
lung	UBERON:0002048	97.89	gold quality
lower esophagus	UBERON:0013473	97.89	gold quality
leukocyte	CL:0000738	97.88	gold quality
left coronary artery	UBERON:0001626	97.86	gold quality
right adrenal gland cortex	UBERON:0035827	97.79	gold quality
vagina	UBERON:0000996	97.75	gold quality
right adrenal gland	UBERON:0001233	97.72	gold quality
left adrenal gland	UBERON:0001234	97.67	gold quality
omental fat pad	UBERON:0010414	97.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.60	gold quality
cortex of kidney	UBERON:0001225	97.58	gold quality
right atrium auricular region	UBERON:0006631	97.56	gold quality
upper lobe of left lung	UBERON:0008952	97.55	gold quality
left adrenal gland cortex	UBERON:0035825	97.54	gold quality
saliva-secreting gland	UBERON:0001044	97.51	gold quality
fundus of stomach	UBERON:0001160	97.50	gold quality
minor salivary gland	UBERON:0001830	97.47	gold quality
adipose tissue	UBERON:0001013	97.44	gold quality
colon	UBERON:0001155	97.42	gold quality
multicellular organism	UBERON:0000468	97.40	gold quality
heart	UBERON:0000948	97.40	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.01

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 145 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	379.7
Caudate putamen	tissue	349.9
Bone marrow	tissue	305.4	high
Cerebral cortex	tissue	233.4	high
Somatosensory cortex	tissue	233.4
Occipital cortex	tissue	226.2
Putamen	tissue	225.8
Postcentral gyrus	tissue	224.3
Cerebellum	tissue	222.1	high
Hippocampal formation	tissue	221.8
Nucleus accumbens	tissue	220.7
Motor cortex	tissue	219.8
Prefrontal cortex	tissue	214.7
Entorhinal cortex	tissue	214.0
Retina	tissue	207.2
Thymus	tissue	206.9
Septum	tissue	206.7
Retrosplenial and cingulate cortex	tissue	205.5
Thalamus	tissue	203.5
Ventral forebrain	tissue	198.5
Basal ganglia	tissue	196.8	high
Temporal cortex	tissue	195.1
Midbrain	tissue	194.9
Olfactory bulb	tissue	194.3
Pons	tissue	194.1
Retrosplenial cortex	tissue	191.5
Ovary	tissue	183.9	high
Superior colliculi	tissue	183.1
Hippocampus	tissue	182.3	high
Thyroid gland	tissue	178.6	high
Hypothalamus	tissue	173.2
Insular cortex	tissue	168.7
Amygdala	tissue	164.8
Corpus callosum	tissue	163.2
Locus coeruleus	tissue	162.1
Tonsil	tissue	159.5	high
Parathyroid gland	tissue	158.8	high
Endometrium 1	tissue	155.9	high
Periaqueductal gray	tissue	154.2
Medulla oblongata	tissue	154.1
Substantia nigra	tissue	152.1
Breast	tissue	150.7	high
Spinal cord	tissue	149.2
Lymph node	tissue	147.6	high
Choroid plexus	tissue	146.4
Kidney	tissue	140.2	high
Cervix	tissue	135.5	high
Smooth muscle	tissue	133.0	high
Seminal vesicle	tissue	125.5	high
Urinary bladder	tissue	124.7	high
Fallopian tube	tissue	123.5	high
Prostate	tissue	122.1	high
Adrenal gland	tissue	120.8	high
Epididymis	tissue	117.2	high
Spleen	tissue	117.2	medium
Placenta	tissue	115.4	high
Lung	tissue	108.7	high
Tongue	tissue	108.4
Gallbladder	tissue	108.1	high
Testis	tissue	107.4	high

Brain sub-regions (HPA Brain Atlas): detected in 380; highest nTPM — Cerebellar cortex (276.0), Perirhinal gyrus (244.2), Nucleus of the diagonal band (238.8), Temporo-occipital transitional zone (237.9), Corpus callosum, genu (white matter) (236.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MATR3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 187 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.122, missense Z 3.96 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000394805 splits into 9 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:139,307,416–139,307,582	30 / 69.5	0.43	no
5:139,307,583–139,307,754	57 / 68.6	0.83	no
5:139,307,755–139,307,806	3 / 21.1	0.14	yes (p 8.0e-05)
5:139,307,807–139,317,617	223 / 334.4	0.67	no
5:139,317,618–139,319,030	32 / 88.0	0.36	no
5:139,319,031–139,319,391	30 / 23.9	1.25	no
5:139,319,392–139,322,653	50 / 133.4	0.37	no
5:139,322,654–139,325,617	215 / 194.7	1.10	no
5:139,325,618–139,329,392	45 / 82.5	0.55	no
DepMap (CRISPR cell-line fitness): dependent in 14.6% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): TTC442 (-1.017), HCE-4 (-1.002), HSC-39 (-0.98), RI-1 (-0.94), PCI-6A (-0.895), SISO (-0.894), CCLF_PEDS_0019_T (-0.87), NB-1 (-0.848), NH-12 (-0.837), EOL-1 (-0.827), SK-N-FI (-0.824), A-375_DAB_TRAM_R (-0.824), MC116 (-0.807), LPS853 (-0.8), NB17 (-0.789).

Literature-anchored findings (GeneRIF, showing 40)

• Data show that the nuclear matrix protein matrin 3, cytoskeletal motor protein HMP, and the circadian clock protein lark were significantly decreased in fetal Down syndrome brain. (PMID:12469345)
• These results suggest that the functions of matrin 3 could be regulated by both Ca(2+)-dependent interaction with calmodulin and caspase-mediated cleavage. (PMID:17658460)
• the spatial proximities among a constellation of functionally related sites that are found within euchromatic regions of the cell nucleus including: HP1gamma, RNA polymerase II, matrin 3, and SAF-A sites (PMID:18618731)
• nonconservative S85C missense mutation in vocal cord and pharyngeal weakness with distal myopathy (PMID:19344878)
• study of the association of matr3 with chromosome territories and identification of potential interacting proteins (PMID:19562669)
• MATR3 to be a novel ATM target in response to DNA damage. (PMID:20421735)
• matrin 3 plays a significant role in controlling cell growth and proliferation (PMID:21182838)
• This study identified no pathogenic mutations in BAG3, MATR3, PTRF or TCAP in Australian muscular dystrophy. (PMID:21683594)
• MATR3 binds viral RNA and is required for the Rev/RRE mediated nuclear export of unspliced HIV-1 RNAs. (PMID:21771346)
• Matrin 3 binds Rev RNA to stabilize HIV-1 transcripts leading to increased cytoplasmic expression. (PMID:21771347)
• Rev needs MATR3 to promote the cytoplasmic accumulation and translation of unspliced RRE-containing mRNA. (PMID:21771348)
• Data suggest that the cellular level of MATR3, known to be highly regulated, modulates the stability of a group of gene transcripts. (PMID:21858232)
• the pY RNA1-s2/Matr3 interaction could play a role in vision (PMID:24558381)
• This study identified mutations in MATR3 in ALS kindreds. also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. (PMID:24686783)
• Sixteen patients from 6 families with late onset distal myopathy associated with the p.S85C MATR3 mutation were characterized. (PMID:25154462)
• Mutations in MATR3 are rare in French familial ALS and ALS with FTLD patients. (PMID:25158920)
• No mutations were identified, indicating that MATR3 mutations are not a common cause of Amyotrophic lateral sclerosis in Australian familial cases with predominately European ancestry (PMID:25523636)
• MATR3 gene disruption is associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus. (PMID:25574029)
• Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB. (PMID:25599992)
• This study shows a high risk of abnormal respiratory function with progressive worsening in MATR3 myopathy. (PMID:25677933)
• MATR3 mutation is identified to be a possible cause of amyotrophic lateral sclerosis. (PMID:25771394)
• Three-dimensional mapping of the lamin A-matrin-3 interface showed that the LMNA truncating mutation Delta303, which lacks the matrin-3 binding domain, was associated with an increased distance between lamin A and matrin-3. (PMID:25948554)
• Suppressing Matrin 3 powers a heightened and broader ZAP restriction of HIV-1 gene expression. (PMID:26129669)
• Its mutations strengthens the role of RNA metabolism in amyotrophic lateral sclerosis etiology. (PMID:26493020)
• Our findings indicate that mutations in Matrin 3 that are associated with ALS and myopathy do not dramatically alter the normal localization of the protein or readily induce inclusion formation. (PMID:26528920)
• It may not be a common genetic factor in Chinese amyotrophic lateral sclerosis patients. (PMID:26708275)
• A missense mutation in MATR3 was identified in myopathy patients undergoing a needle electromyography. (PMID:26899464)
• Depletion of SAFB1 reduced FUS’s localization to chromatin-bound fraction and splicing activity, suggesting SAFB1 could tether FUS to chromatin compartment thorough N-terminal DNA-binding motif. Moreover, FUS interacts with another nuclear matrix-associated protein, Matrin3. (PMID:27731383)
• Using a novel RNA pulldown approach that utilized endogenous S1-tagged PINCR (a p53-regulated long noncoding RNA), the authors show that PINCR associates with the enhancer region of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. (PMID:28580901)
• Matrin3 physically interacts with intronic pyrimidine-rich sequences and controls alternative splicing. (PMID:28695676)
• The intra-nuclear localization and interaction network of MATR3 is strongly modulated by its RRM2 domain. (PMID:29511296)
• This might contribute to cellular damage and progression of dystrophy in muscle of Matrin-3 myopathy (PMID:29763601)
• cytoplasmic MATR3 redistribution mitigated neurodegeneration, suggesting that nuclear MATR3 mediates toxicity. (PMID:30015619)
• PTBP1 and MATR3 co-bind and repress RNA processing within and around young LINEs (PMID:30078707)
• FUS, EWSR1, TAF15 and MATR3 within the RNAP II/U1 snRNP machinery play distinct roles in the development of amyotrophic lateral sclerosis and spinal muscular atrophy that are more intimately tied to one another than previously thought. (PMID:30398641)
• In this work we identify the cellular protein MATR3 as an essential cofactor of viral RNA processing. Reactivation of HIV-1 transcription is not sufficient to allow completion of a full life cycle of the virus if MATR3 is depleted. (PMID:30425153)
• identified MATR3 as binding to SNHG1 and the interaction might be involved in splicing events that enhance neuroblastoma progression. (PMID:30516047)
• The data of this study suggest that MATR3 may have regulatory mechanisms that are influenced by tissue type and/or mutation status (PMID:30563574)
• Data shows the expression profile of Gle1, MATR3 and FUS genes in Spinal muscular atrophy (SMA), and suggest a critical role of FUS protein in SMA pathogenesis. Note that the authors appear to erroneously refer to the human MATR3 gene (GeneID: 9782) as MART3 (GeneID: 203430) in this publication. (PMID:30565205)
• MATR3 regulates miR-138 in neurons, with important implications for miR-138 regulation during neuronal development, synaptic plasticity and memory-related processes. (PMID:30790622)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	matr3l1.2	ENSDARG00000000394
danio_rerio	si:ch211-271b14.1	ENSDARG00000101808
mus_musculus	Matr3	ENSMUSG00000037236
rattus_norvegicus	Matr3	ENSRNOG00000019875

Paralogs (1): ZNF638 (ENSG00000075292)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1298379) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 40 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart valve morphology	1
small cerebellum	1
Purkinje cell degeneration	1
abnormal neuromuscular synapse morphology	1
decreased body weight	1
weight loss	1
decreased body size	1
ataxia	1
impaired coordination	1
limb grasping	1
impaired righting response	1
cyanosis	1
respiratory distress	1
premature death	1
decreased vertical activity	1
patent ductus arteriosus	1
astrocytosis	1
aorta coarctation	1
abnormal aortic arch morphology	1
interrupted aortic arch	1
axon degeneration	1
decreased skeletal muscle fiber size	1
impaired contextual conditioning behavior	1
impaired cued conditioning behavior	1
axonal spheroids	1

+15 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	Q29099	98.4%	Diamond
Bos taurus	Q8WN55	98.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNORA74D	snoRNA	109616975
SIL1-AS1	ncRNA	124901080
SIL1	protein-coding	64374
SNHG4	ncRNA	724102
SNORA74A	snoRNA	26821
PAIP2	protein-coding	51247
SLC23A1	protein-coding	9963
MZB1	protein-coding	51237
SPATA24	protein-coding	202051
PROB1	protein-coding	389333
CTNNA1-AS1	ncRNA	105379194
CTNNA1	protein-coding	1495
LRRTM2	protein-coding	26045

Protein

Protein identifiers

Matrin-3 — P43243 (reviewed: P43243)

All UniProt accessions (21): P43243, A0A0R4J2E8, A0A1B0GX04, A8MXP9, B3KM87, D6R8Z5, D6R991, D6R9F3, D6R9N0, D6RAM9, D6RAY2, D6RB45, D6RBI2, D6RBK5, D6RBS2, D6RCM3, D6RE02, D6REK4, D6REM6, D6RIA2, H0Y8T4

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs. May bind to specific miRNA hairpins.

Subunit / interactions. Part of a complex consisting of SFPQ, NONO and MATR3. Interacts with AGO1 and AGO2. Part of a complex composed at least of ASH2L, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with TARDBP. Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA. Interacts with FUS. Interacts with IGF2BP1; the interaction is enhanced by SEPIN14P20 peptide RBPR. Interacts with IGF2BP2 and IGF2BP3. Interacts with RBPMS.

Subcellular location. Nucleus matrix.

Disease relevance. Amyotrophic lateral sclerosis 21 (ALS21) [MIM:606070] A neurodegenerative disorder affecting upper and lower motor neurons, resulting in muscle weakness and respiratory failure. Some patients may develop myopathic features or dementia. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
P43243-1	1	yes
P43243-2	2

RefSeq proteins (31): NP_001181883, NP_001181884, NP_001181885, NP_001269207, NP_001387370, NP_001387371, NP_001387372, NP_001387373, NP_001387374, NP_001387376, NP_001387377, NP_001387379, NP_001387380, NP_001387381, NP_001387382, NP_001387383, NP_001387384, NP_001387385, NP_001387386, NP_001387387, NP_001387388, NP_001387389, NP_001387390, NP_001387391, NP_001387392, NP_001387393, NP_001387394, NP_001387395, NP_001387396, NP_061322, NP_954659 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR000690	Matrin/U1-C_Znf_C2H2	Domain
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034928	MATR3_RRM1	Domain
IPR034930	MATR3_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

UniProt features (94 total): modified residue 44, cross-link 18, sequence variant 9, compositionally biased region 7, sequence conflict 5, region of interest 4, domain 2, initiator methionine 1, chain 1, zinc finger region 1, splice variant 1, short sequence motif 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43243-F1	57.64	0.02

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH supported · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (62)

Type	Positions
N-acetylserine	2
N6-acetyllysine	3, 522, 571, 836
Phosphoserine	4, 9, 11, 14, 22, 41, 118, 126, 157, 164, 188, 195, 206, 208, 211, 234, 264, 275, 509, 511, 533, 596, 598, 604, 606, 654, 671, 673, 674, 689, 747, 759, 766
Phosphothreonine	150, 679, 741
Phosphotyrosine	158, 202, 219
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	3, 132, 146, 245, 269, 478, 487, 491, 515, 522, 554, 555, 617, 630, 719, 736, 770, 836

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 378 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_BLASTOCYST_FORMATION, GGCNKCCATNK_UNKNOWN, ATGTTAA_MIR302C, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, SRF_C, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT

GO Biological Process (6): activation of innate immune response (GO:0002218), heart valve development (GO:0003170), ventricular septum development (GO:0003281), post-transcriptional regulation of gene expression (GO:0010608), innate immune response (GO:0045087), immune system process (GO:0002376)

GO Molecular Function (8): RNA binding (GO:0003723), structural molecule activity (GO:0005198), zinc ion binding (GO:0008270), miRNA binding (GO:0035198), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nuclear inner membrane (GO:0005637), membrane (GO:0016020), nuclear matrix (GO:0016363)

GO top-level categories

22 GO namespaces:

Category	Terms
binding	2
cellular anatomical structure	2
activation of immune response	1
positive regulation of innate immune response	1
heart development	1
animal gross anatomical part developmental process	1
cardiac ventricle development	1
cardiac septum development	1
regulation of gene expression	1
immune response	1
defense response to symbiont	1
biological_process	1
nucleic acid binding	1
molecular_function	1
transition metal ion binding	1
regulatory RNA binding	1
protein binding	1
cation binding	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
nuclear membrane	1
nuclear lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
activation of innate immune response	BP	direct assay
post-transcriptional regulation of gene expression	BP	direct assay
membrane	CC	high-throughput assay
RNA binding	MF	high-throughput assay
identical protein binding	MF	physical interaction
miRNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,222 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MATR3	SLC23A1	Q9UHI7	845
MATR3	SLC23A2	Q9UGH3	844
MATR3	TARDBP	Q13148	730
MATR3	FUS	P35637	726
MATR3	HNRNPA2B1	P22626	725
MATR3	ATXN2	Q99700	723
MATR3	HNRNPA1	P09651	715
MATR3	C9orf72	Q96LT7	706
MATR3	CHCHD10	Q8WYQ3	701
MATR3	UBQLN2	Q9UHD9	679
MATR3	VCP	P55072	669
MATR3	NEK1	Q96PY6	660
MATR3	SETX	Q7Z333	645
MATR3	DCTN1	Q14203	643
MATR3	TIA1	P31483	636

IntAct

Human interaction partners of MATR3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 48 partners by confidence:

Partner	Interaction type	MIscore	Records
FUS	association	0.730	3
RASD1	physical association	0.720	6
HNRNPK	physical association	0.670	7
HTT	physical association	0.670	3
RBM45	physical association	0.580	2
TARDBP	physical association	0.560	6
PTBP2	physical association	0.560	4
KRT27	physical association	0.560	3
KRT34	physical association	0.560	3
PCBP3	physical association	0.560	3
PLEKHG4	physical association	0.560	3
TRAF1	physical association	0.560	3
TSGA10	physical association	0.560	3
HTR7	physical association	0.560	1
EGFR	physical association	0.550	2
DZIP3	physical association	0.400	1
FKBPL	physical association	0.400	1
FLII	physical association	0.400	1
GALNT11	physical association	0.400	1
HNRNPA1L2	physical association	0.400	1
IL1R1	physical association	0.400	1
ILKAP	physical association	0.400	1
MCTP1	physical association	0.400	1
PROC	physical association	0.400	1
RAPH1	physical association	0.400	1
RNF166	physical association	0.400	1
S100A4	physical association	0.400	1
SGIP1	physical association	0.400	1
TRIM2	physical association	0.400	1
ZKSCAN1	physical association	0.400	1

BioGRID (928 interactions; top human partners by supporting records in a sample of 600 records): HNRNPK (Two-hybrid; 7 records), HNRNPA1 (Affinity Capture-MS; 6 records), PTBP3 (Affinity Capture-MS; 4 records), ADAR (Affinity Capture-MS; 3 records), BRD4 (Affinity Capture-MS; 3 records), DDX17 (Affinity Capture-MS; 3 records), DDX3X (Affinity Capture-MS; 3 records), DDX5 (Affinity Capture-MS; 3 records), DHX9 (Affinity Capture-MS; 3 records), ELAVL1 (Affinity Capture-MS; 3 records), FUBP3 (Affinity Capture-MS; 3 records), FUS (Affinity Capture-MS; 3 records), HNRNPA0 (Affinity Capture-MS; 3 records), HNRNPA2B1 (Affinity Capture-MS; 3 records), HNRNPA3 (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
FUS	“up-regulates activity”	MATR3	relocalization

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
★ SNW1 complex	18	SNW1, TUBB, ABCF2, DDB1, DDX23, EEF1A1, HSPA5, PFKL, CDC5L, EFTUD2, PRPF8, SFPQ, MATR3, MSH2, UBR5, EEF1G, HNRNPU, SNRNP200
HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex	9	MATR3, NONO, PRKDC, RBM14, HEXIM1, PSPC1, SFPQ, XRCC5, XRCC6
p54(nrb)-PSF-matrin3 complex	3	MATR3, NONO, SFPQ

Disease & clinical

Genetic variants

Variant evidence for MATR3: 627 ClinVar records (1 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

627 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	314
Likely benign	213
Benign	48

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
14002	NM_018834.6(MATR3):c.254C>G (p.Ser85Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	8

Per-variant reference — Sugi Variant

Explore MATR3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 1,192):

Position(s)	Effect	Δscore	Sites
5:139316059	acceptor_gain	1.0000
5:139316067	acceptor_gain	1.0000
5:139316074–139316075	acceptor_loss	1.0000	5
5:139316189–139316190	donor_loss	1.0000	5
5:139317588–139317590	acceptor_gain	1.0000	4
5:139317595	acceptor_loss	1.0000	2
5:139317722–139317723	donor_loss	1.0000	4
5:139318906–139318907	acceptor_loss	1.0000	5
5:139319034–139319035	donor_loss	1.0000	5
5:139319319	acceptor_gain	1.0000

AlphaMissense

2,715 missense substitutions predicted likely pathogenic (of 5,627 scored), across 588 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M529	9	0.980	1.000
M441	9	0.962	1.000
M539	9	0.940	1.000
M403	9	0.930	0.994
M548	9	0.927	0.999
D280	8	0.999	1.000
H309	8	0.999	1.000
H820	8	0.999	1.000
H826	8	0.999	1.000
D121	8	0.998	1.000
H315	8	0.998	1.000
H401	8	0.998	1.000
F438	8	0.996	1.000
F536	8	0.996	1.000
F809	8	0.992	1.000
F405	8	0.991	1.000
F422	8	0.991	1.000
D510	8	0.991	0.999
F559	8	0.991	1.000
F115	8	0.990	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

6 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.2e-09
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	9.69e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000114
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000582
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000643
Rectum Adenocarcinoma (TCGA)	favorable	0.00089

Disease associations

OMIM: gene MIM:164015 | disease phenotypes: MIM:606070

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
distal myopathy with vocal cord weakness	Definitive	Autosomal dominant	2
amyotrophic lateral sclerosis type 21	Strong	Autosomal dominant	4
amyotrophic lateral sclerosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
distal myopathy with vocal cord weakness	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

Panel	Rating
Distal myopathies	green
Hypotonic infant	green
Other rare neuromuscular disorders	green
Adult-onset neurological disorders	amber
Neurodegenerative disorders, adult onset	amber

Mondo (3): amyotrophic lateral sclerosis type 21 (MONDO:0011632), distal myopathy with vocal cord weakness (MONDO:0018951), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (2): Vocal cord and pharyngeal distal myopathy (Orphanet:600), Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

showing 60 of 85 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000217	Xerostomia
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0000762	Decreased nerve conduction velocity
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001283	Bulbar palsy
HP:0001288	Gait disturbance
HP:0001308	Tongue fasciculations
HP:0001347	Hyperreflexia
HP:0001430	Abnormal calf musculature morphology
HP:0001604	Vocal cord paresis
HP:0001609	Hoarse voice
HP:0001611	Hypernasal speech
HP:0001618	Dysphonia
HP:0001621	Weak voice
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002094	Dyspnea
HP:0002127	Abnormal upper motor neuron morphology
HP:0002145	Frontotemporal dementia
HP:0002180	Neurodegeneration
HP:0002307	Drooling
HP:0002313	Spastic paraparesis
HP:0002317	Unsteady gait
HP:0002360	Sleep disturbance
HP:0002366	Abnormal lower motor neuron morphology
HP:0002380	Fasciculations
HP:0002460	Distal muscle weakness
HP:0002463	Language impairment
HP:0002483	Bulbar signs
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0002835	Aspiration
HP:0002878	Respiratory failure
HP:0002936	Distal sensory impairment
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase activity
HP:0003324	Generalized muscle weakness
HP:0003376	Steppage gait
HP:0003394	Muscle spasm
HP:0003457	EMG abnormality
HP:0003470	Paralysis
HP:0003484	Upper limb muscle weakness
HP:0003487	Babinski sign
HP:0003547	Shoulder girdle muscle weakness
HP:0003557	Increased variability in muscle fiber diameter
HP:0003581	Adult onset
HP:0003596	Middle age onset
HP:0003687	Centrally nucleated skeletal muscle fibers
HP:0003693	Distal amyotrophy
HP:0003738	Exercise-induced myalgia
HP:0003805	Rimmed vacuoles
HP:0004326	Cachexia
HP:0005934	Imperfect vocal cord adduction
HP:0007149	Distal upper limb amyotrophy
HP:0007340	Lower limb muscle weakness

GWAS associations

4 associations:

Study	Trait	p-value
GCST010725_43	Malaria	4e-7
GCST005951_96	Body mass index	6e-7
GCST009391_2121	Metabolite levels	2e-6
GCST010725_82	Malaria	2e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010382	phosphatidylcholine 36:4 measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724643 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (3 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

3 potent at pChembl≥5 of 5 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.64	Kd	22.66	nM	CHEMBL5653589
7.64	ED50	22.66	nM	CHEMBL5653589
6.80	IC50	160	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148724: Binding affinity to human MATR3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0227	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178814: Inhibition of MATR3 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.1600	uM

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	3
Valproic Acid	increases expression, decreases expression	3
methylmercuric chloride	increases expression	2
trichostatin A	affects cotreatment, decreases expression, affects expression	2
sodium arsenite	decreases expression	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	2
Doxorubicin	affects expression, increases expression	2
Cadmium Chloride	decreases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
afimoxifene	decreases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
acyline	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651766	Binding	Binding affinity to human MATR3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

13 cell lines: 10 induced pluripotent stem cell, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4CT	BNIi001-A	Induced pluripotent stem cell	Male
CVCL_A4CU	BNIi001-B	Induced pluripotent stem cell	Male
CVCL_D1HX	HAP1 MATR3 (-) 1	Cancer cell line	Male
CVCL_D1HY	HAP1 MATR3 (-) 2	Cancer cell line	Male
CVCL_D1HZ	HAP1 MATR3 (-) 3	Cancer cell line	Male
CVCL_E4U4	KOLF2.1J MATR3 24.0kbdel DEL/WT	Induced pluripotent stem cell	Male
CVCL_E7LG	KOLF2.1J MATR3 F115C SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7LH	KOLF2.1J MATR3 F115C SNV/WT	Induced pluripotent stem cell	Male
CVCL_E7LJ	KOLF2.1J MATR3 S85C SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E7LK	KOLF2.1J MATR3 S85C SNV/WT	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00542412	Phase 4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	Phase 4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	Phase 4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	Phase 4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	Phase 4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	Phase 4	ACTIVE_NOT_RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	Phase 3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	Phase 3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	Phase 3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	Phase 3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	Phase 3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	Phase 3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	Phase 3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	Phase 3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	Phase 3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	Phase 3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	Phase 3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	Phase 3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	Phase 3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	Phase 3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	Phase 3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	Phase 3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	Phase 3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	Phase 3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	Phase 3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	Phase 3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	Phase 3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	Phase 3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	Phase 3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	Phase 3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	Phase 3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	Phase 3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	Phase 3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	Phase 3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	Phase 3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	Phase 3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	Phase 3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	Phase 3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04577404	Phase 3	COMPLETED	Safety Extension Study of Oral Edaravone Administered in Subjects With Amyotrophic Lateral Sclerosis (ALS)
NCT04745299	Phase 3	COMPLETED	Evaluation the Efficacy and Safety of Mutiple Lenzumestrocel (Neuronata-R® Inj.) Treatment in Patients With ALS
NCT04768972	Phase 3	ACTIVE_NOT_RECRUITING	FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)
NCT04944784	Phase 3	TERMINATED	A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT05021536	Phase 3	UNKNOWN	Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment
NCT05151471	Phase 3	TERMINATED	Efficacy and Safety Extension Study of Oral Edaravone Administered in Subjects With ALS
NCT05178810	Phase 3	COMPLETED	Study to Investigate the Efficacy and Safety of FAB122 (Daily Oral Edaravone) in Patients With Amyotrophic Lateral Sclerosis
NCT05193994	Phase 3	TERMINATED	Triumeq in Amyotrophic Lateral Sclerosis
NCT05442775	Phase 3	TERMINATED	A Phase 3, Open-Label Extension of COURAGE-ALS (CY 5031)
NCT05568615	Phase 3	COMPLETED	Extension Study Following the Studies MT-1186-A03 or A04 to Evaluate the Safety of Oral Edaravone in Subjects With ALS
NCT05619783	Phase 3	COMPLETED	Extension Study Evaluating The Safety And Tolerability of AMX0035
NCT05753852	Phase 3	UNKNOWN	Open Label Extension of TUDCA-ALS Study
NCT05866926	Phase 3	TERMINATED	Study to Investigate the Long-term Safety of FAB122 in Patients With Amyotrophic Lateral Sclerosis
NCT06008249	Phase 3	TERMINATED	Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)
NCT06658977	Phase 3	TERMINATED	RolloverTreatment With Triumeq for People With ALS Following the Lighthouse II Trial
NCT06973629	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of MSC-NTF (NurOwn) in Participants With Early Symptomatic ALS and Moderate Disease Presentation in ALS (ENDURANCE STUDY)
NCT07174492	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of Masitinib in Combination With SoC Versus Placebo in the Treatment of ALS Patients
NCT07322003	Phase 3	RECRUITING	Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS
NCT00004771	Phase 2	COMPLETED	Phase II Study of Leuprolide and Testosterone for Men With Kennedy’s Disease or Other Motor Neuron Disease
NCT00005674	Phase 2	COMPLETED	Clinical Trial of Creatine in Amyotrophic Lateral Sclerosis [ALS]

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MATR3 across ~30M SureChEMBL compounds — explore on Sugi Predict.